Advances in the field of biotechnology have led to significant advances in the treatment of diseases such as cancer, genetic diseases, arthritis and AIDS that were previously difficult to treat. Many such advances involve the administration of oligonucleotides and other nucleic acids to a subject, particularly a human subject. The administration of such molecules via parenteral routes has been shown to be effective for the treatment of diseases and/or disorders. See, e.g., Draper et al., U.S. Pat. No. 5,595,978, Jan. 21, 1997, which discloses intravitreal injection as a means for the direct delivery of antisense oligonucleotides to the vitreous humor of the mammalian eye. See also, Robertson, Nature Biotechnology, 1997, 15, 209, and Genetic Engineering News, 1997, 15, 1, each of which discuss the treatment of Crohn's disease via intravenous infusions of antisense oligonucleotides. Non-parenteral routes for administration of oligonucleotides and other nucleic acids (such as oral or rectal delivery or other mucosal routes) offers the promise of simpler, easier and less injurious administration of such nucleic acids without the need for sterile procedures and their concomitant expenses, e.g., hospitalization and/or physician fees. There thus is a need to provide compositions and methods to enhance the availability of novel drugs such as oligonucleotides when administered via non-parenteral routes. It is desirable that such new compositions and methods provide for the simple, convenient, practical and optimal non-parenteral delivery of oligonucleotides and other nucleic acids.
Pouchitis is the most frequent long-term complication of ileal pouch-anal anastomosis for ulcerative colitis. A variety of pathophysiologic mechanisms have been proposed but the precise pathogenesis remains unknown. The incidence of a first episode of pouchitis at 1, 5 and 10 years post-operatively is about 15%, 33% and 45%, respectively (Svaninger et al., Scand. J. Gastroenterol. 28:695, 1993; Penna et al., Gut 38:234, 1996). Two-thirds of pouchitis cases recur, manifest either as acute relapsing pouchitis (three-fourths of those who recur) or chronic, unremitting pouchitis (one-fourth of the recurrent population). Half of the chronic, unremitting pouchitis population will eventually require surgical treatment of the pouch (Sandborn, in Trends in Inflamatory Bowel Disease, McLeod et al, eds., Kluwer Academic Publishers, Lancaster, UK, pp. 51-63, 1997).
Present pouchitis treatments consist mainly of antibiotics, aminosalicylates and steroids. Antibiotics appear to be effective for acute pouchitis. For patients with chronic, recurrent or chronic, unremitting pouchitis, therapeutic options are less satisfactory. Chronic administration of metronidazole at a high dose of 20 mg/kg/day can cause symptomatic peripheral neuropathology in up to 85% of patients. This can be a limiting factor in using maintenance metronidazole to suppress chronic pouchitis (Tremaine et al., Aliment. Pharmacol. Ther. 11:1041-1046, 1997). Long-term steroid therapy, even by enema administration, is associated with well-known side effects. The result is that patients not responsive to these agents have few options other than to tolerate chronic symptoms or undergo surgical takedown of their pouch and return to an externalized ileostomy.